The general objective of this project is to investigate further the structure and function of plasma and platelet factor XIII and to relate these to the action of factor XIII in physiologic and pathologic processes. Factor XIII is the proenzyme which, in its activated state, participates in the terminal phase of the coagulation of blood and catalyzes the chemical crosslinking of fibrin. Development of radioimmunoassays for the subunits of the zymogen and for the active enzyme are an important part of this project. These RIAs have been used to study the control of expression of the factor XIII subunits in plasma and to correlate factor XIII activity with a and b subunit concentrations in vivo. These experiments indicate that the plasma level of functional a chain controls the plasma b chain concentration. In other studies on factors which control the metabolism of factor XIII it has been shown that plasmin has no effect on either the factor XIII zymogens or the enzyme. Platelet factor XIII can be labeled during in vivo synthesis in megakaryocytes by infusion of labeled amino acids into canine bone marrow.